This test is for individuals with a clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT). The primary Invitae Hereditary Hemorrhagic Telangiectasia Panel includes four genes that are definitively associated with HHT.
Individuals with clinical symptoms of HHT may benefit from diagnostic genetic testing to establish or confirm diagnosis, clarify risks, or inform management. Asymptomatic members of a family with a known HHT pathogenic variant may also benefit by avoiding specific medications (e.g., anticoagulation and anti-inflammatory agents) that can trigger symptoms.
ACVRL1 ENG GDF2 RASA1 SMAD4
ACVRL1 ENG GDF2 RASA1 SMAD4
Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia characterized by the presence of multiple arteriovenous malformations (AVMs), an abnormality of the development of arterial and venous vessels, which result in direct connections between arteries and veins due to the lack of intervening capillaries. Small AVMs that occur near the skin surface and are markedly visible are known as telangiectasias. Individuals with HHT are at risk for spontaneous and recurrent nosebleeds (epistaxis) and hemorrhages in the brain, liver, lungs, or other organs.
This test covers the most common genetic causes of HHT. Pathogenic variants in ENG and ACVRL1 account for 60%-80% of clinical HHT cases. The remaining genes on this panel account for an unknown proportion of HHT cases.
HHT is an autosomal dominant condition.
HHT exhibits age-related penetrance, meaning individuals who inherit a predisposition to develop HHT will have an increased manifestation of symptoms over their lifetime. Most individuals with HHT present with age-related symptoms, typically occurring at or after adolescence. Because HHT is a developmental disorder, severely affected infants have also been reported. Variable expression has been reported within families as well.
The prevalence of HHT is between 1 in 5,000 and 1 in 10,000 people.
This test may be considered for individuals with:
For links to published management guidelines, please refer to our Management guidelines page.
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|